Oxidation of a-Amino Alcohols

The hydrochlorides of esters of glycine and alanine have been reduced with sodium amalgam to the amino carbonyl compounds and then oxidized with mercuric chloride in an excess of alkali to yield pyrazine and 2,5-dimethylpyrazine, respectively (255,256). 

Reaction of a-Hydroxy Carbonyl Compounds or Polyhydroxy Compounds with Ammonia, Ammonium Salts, or Formamide 

Some a-hydroxy carbonyl compounds when heated with ammonia, ammonium acetate or formate, or formamide have been shown to give pyrazines the reaction presumably proceeds through the a-amino carbonyl compound. 

This reaction was first applied by Erdmann (11) to the preparation of tetra-phenylpyrazine by heating benzoin (PhCHOHCOPh) with ammonia. The reaction of benzoin with ammonium acetate in glacial acetic acid has been investigated by Davidson et al. (257), and it has been shown that identical results were obtained when the benzoin was replaced by desylamine (PhCHNH2COPh). 

Some pyrazines prepared by this method are listed in Table II.4 (3,11,12,205, 257-267). 

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A classical synthesis of alkyl- and arylpyrazines involves dimerization of a-amino carbonyl compounds, which may be produced by many methods such as reduction of a-oximino ketones, aminolysis of a-halogeno ketones (Section 6.0T11.2), oxidation of a-amino alcohols and reduction of a-amino acids . The condensation of 1,2-diamines with a-dicarbonyl compounds is available for the synthesis of particularly quinoxaline derivatives (Section 6.03.11.1). The synthetic methods which rely on self-condensation, however, provide only symmetrically substituted pyra-... 

An improved preparation of (S)-N-(Boc)-cyclohexylalaninal by application of the Moffatt-Swern oxidation of a-amino alcohols has been described [1346]. MofFatt-Swern oxidation of protected (S)-alcohol 1803 with DMSO/(COCl)2/Et3N/... 

The mechanism for the oxidative photofragmentation of a,/ -amino alcohols is consistent with a preference for anti geometry in the cleavage step (Ci, X. Kellett, M. A. Whitten, D. G., J. Am. Chem. Soc., 1991, 113, 3893). Provide a rationalization based on the frontier orbitals of the system. 

Table 4 Preparation of N°-Protected a-Amino Aldehydes by Oxidation of P-Amino Alcohols 1032-37-42 ...

Swem oxidation of /1-amino alcohols has been shown to be a useful alternative to metal-based oxidants, which may be chelated by the substrate.115 A - VIethylpyrrolidine, A-ethylpiperidine. or triethylamine proved optimal as bases. The reaction, although successful for /1-secondary amino alcohols, gave products that readily polymerized. 

Glutamate, which now contains the nitrogen atom of the former amino acid, next undergoes an o. idative denmin-atjort to yield ammonJum ion and regerseraced u-ketc lutarate. The oxidation of the amine to an imine ii mechanistically similar to the oxidation of a secondary alcohol to a ketone and is carried out by NAD. The imine is then hydrolyzed in the usual way. 

Similarly, diisopropylamine is sometimes substituted for Et3N owing to its more hindered nature. Occasionally however, neither of these bases will provide the optimum yield for a reaction, as shown by Chrisman and Singaram," A range of bases were compared in the oxidation of p-amino alcohols, such as 13. The results are tabulated. 

The reagent potassium nitrosodisulfonate (33), known as Fremy s salt, was first prepared in 1845. Its use as a chemoselective oxidizing agent has been reviewed extensively by Zimmer [59a] and Parker [59b] and will only be mentioned briefly here. While it is most widely known for its use in the oxidation of various heteroatom-substituted aromatic compounds to quinones [59], it has also been used in the selective oxidation of benzylic alcohols to ketones [60] and the oxidation of a-amino and a-hydroxy acids to a-keto acids [61]. 

Reduction of the ketolactam 390 (having the newly assigned A/B trans stereochemistry) with sodium borohydride followed by reduction of the amide with lithium aluminum hydride gave an amino alcohol. Oxidation of this amino alcohol with chromic acid followed by rereduction with lithium aluminum hydride gave an amino alcohol different from that obtained previously. In the oxidation to the ketone 373, therefore, epimerization at C-9a must have occurred, and the two amine alcohols must have the configurations 391 and 392. Since in both compounds Bohlmann bonds were observed in the IR spectrum, the A/ ring juncture is trans. 

The effect of different amine bases on the Swern oxidation of y6-amino alcohols has been studied. Swern oxidation of 6-amino alcohols containing tertiary amino groups afforded the corresponding a-amino carbonyl compounds in fair to excellent yields. Yields were dependent on the steric requirement of the amine base used for the reaction and were optimized by the use of N-methylpyrrolidine, N-ethylpiperidine, or triethylamine, depending on the yS-amino alcohol substrate [1380]. 

Oxidation of aryloxy amino alcohols 1854 with activated DMSO provided a convenient one-pot method for synthesizing hydroxyimines 1856 without isolation of the unstable intermediate ketones 1855 [1387]. Assignment of the (Z)- and ( )-... 

Reaction of dibenzylamine with ethylene oxide affords the amino alcohol, 82. Treatment of that product with thionyl chloride gives the a-sympathetic blocking agent, dibenamine (83). (Condensation of phenol with propylene chlorohydrin (84) gives the alcohol, 85. Reaction with thionyl chloride affords the chloride (86). Use of the halide to alkylate ethanolamine affords the secondary amine (87). Alkylation of this last with benzyl chloride... 

In a process related to the Knorr pyrrole synthesis, condensation of p-amino alcohols 10 with p-dicarbonyl compounds 11 affords p-hydroxy enamines 12 which are then oxidized to the pyrroles 13 <96TL9203>. 

Geoghegan, K.E, and Stroh, J.G. (1992) Site-directed conjugation of nonpeptide groups to peptides and proteins via periodate oxidation of a 2-amino alcohol. Applications to modification at N-terminal serine. Bioconjugate Chem. 3, 138-146. 

The pyridoxal amino acid analog (Pal) was stereoselectively synthesized from a readily available pyridoxol derivative and the residue was incorporated into peptides at the alcohol oxidation state in protected form. Oxidation of the 4 -alcohol group to the desired aldehyde was achieved post-synthetically on free. 

The oxidation of propargyl alcohol to the acid and of but-2-yne-l,4-diol to acetylene dicarboxylic acid is carried out on a technical scale at a lead dioxide anode in sulphuric acid [4, 5]. Electrochemical oxidation of acetylenic secondary alcohols to the ketone at lead dioxide in aqueous sulphuric acid [4], gives better results than the cliromic acid based process of Jones [6], Oxidation of aminoalkan-1-ols to the amino acid at a lead dioxide anode in sulphuric acid is achieved in 31 -73 % 5delds [7]. This route is applied to the technical scale production of (l-alanine from 3-aminopropanol in an undivided cell [8]. 

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